Anti-CGRP treatment for Migraines

Discovered in 1982, CGRP was found to be produced from the same gene that produces calcitonin, a hormone involved in regulating calcium levels in the body. Researchers quickly realized that CGRP acts as a neuropeptide, primarily found in nerve cells, and plays a role in various bodily functions such as pain sensation, regulating blood pressure, and controlling gastrointestinal functions.

Relationship between CGRP and Migraine

Current research strongly suggests that CGRP plays a crucial role in the onset of acute migraine attacks.

1. Traditionally, migraine episodes were attributed to the dilation of brain blood vessels. However, investigations on both animals and human brain vessels have demonstrated that CGRP relaxes these vessels, potentially impacting blood flow.
2. Further experiments involving cats and humans have revealed that stimulating specific nerves in the head can trigger the release of CGRP into the bloodstream.
3. Additionally, studies have found that drugs like Sumatriptan, commonly used to alleviate migraines, can effectively reduce CGRP levels in the blood.
4. Notably, direct infusion of CGRP into the bloodstream has been shown to induce symptoms similar to migraines.

Medications that act directly on the CGRP Pathway

The identification of the significant association between CGRP and migraines spurred the creation of designer drugs tailored to target CGRP and its receptors. In 2018, the FDA (Food and Drug Administration of the United States) greenlit Erenumab as the pioneering anti-CGRP treatment for migraines. Currently, medications targeting the CGRP can be divided into two classes:

CGRP receptor antagonists
Gepants are a class of medications designed to treat migraines. These drugs work by targeting the CGRP receptor, which is involved in the transmission of pain signals and the dilation of blood vessels associated with migraines. By blocking the CGRP receptor, gepants prevent CGRP from binding to it and exerting its effects. This helps reduce inflammation and pain, ultimately providing relief from migraine symptoms. Gepants are typically taken orally and are used for both acute treatment of migraine attacks and prevention of migraines.

CGRP Monoclonal antibodies
CGRP monoclonal antibodies, known as zumabs, are a type of medication that directly target CGRP itself. Monoclonal antibodies are laboratory-produced molecules that mimic the immune system's ability to fight off harmful substances. CGRP monoclonal antibodies are designed to bind to CGRP molecules circulating in the body, preventing them from interacting with their receptors. By blocking CGRP, these medications reduce the release of inflammatory substances and help alleviate migraine symptoms. CGRP monoclonal antibodies are usually administered via injection and are used for the prevention of migraines rather than for acute treatment.

What should I expect when taking an Anti-CGRP medication?

These medications aim to reduce the frequency, severity, and duration of migraine attacks. Depending on the specific medication prescribed, you may experience relief within hours for acute attacks (gepants) or over several weeks to months for preventive treatment (zumabs).
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CGRP monoclonal antibodies are commonly administered through injections, either subcutaneously (under the skin) such as Erenumab, Fremanezumab, and Galcanezumab, or intravenously like Eptinezumab. It's essential to recognize that these medications don't provide immediate relief. The timeframe for their effectiveness can vary widely among individuals. While some patients may experience improvement within a week of treatment initiation, others may require up to 6 months to observe noticeable benefits. As a result, it's generally advisable to continue treatment for approximately 6 months to gauge its full impact.

What happens if I don't get better with Anti-CGRPs?

If you find that anti-CGRP medications are not providing the desired relief for your migraines, there are several alternative treatment options that your healthcare provider may recommend. This can include switching to another anti-CGRP medication, CGRP antagonist, or considering the use of BTX or nerve blocks for migraine treatment.

​Additionally, your healthcare provider may suggest combining treatments or incorporating lifestyle modifications to enhance your migraine management. This could involve implementing stress management techniques, making dietary changes, engaging in regular exercise, ensuring adequate sleep, and identifying and avoiding migraine triggers.


Dr Christopher Liu is a Pain Specialist based at Napier Pain Specialists @ Gleneagles Hospital, Singapore. For more information on his practice, click here.